Non-culprit left main coronary artery disease in acute myocardial infarction complicated by cardiogenic shock

Objectives We evaluated the clinical impact of residual non-culprit left main coronary artery disease (LMCAD) on prognosis in patients undergoing emergent percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). Methods A total of 429 patients who underwent PCI for AMI complicated by CS was enrolled from 12 centers in the Republic of Korea. The patients were divided into two groups according to presence of non-culprit LMCAD or not: the LMCAD non-culprit group (n = 43) and the no LMCAD group (n = 386). Primary outcome was major adverse cardiac event (MACE, defined as a composite of cardiac death, myocardial infarction, or repeat revascularization). Propensity score matching analysis was performed to reduce selection bias and potential confounding factors. Results During a 12-month follow-up, a total of 168 MACEs occurred (LMCAD non-culprit group, 17 [39.5%] vs. no LMCAD group, 151 [39.1%]). Multivariate analysis revealed no significant difference in the incidence of MACE at 12 months between the LMCAD non-culprit and no LMCAD groups (adjusted hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.58 to 1.62, p = 0.901). After propensity score matching, the incidence of MACE was still similar between the two groups (HR 0.64; 95% CI 0.33 to 1.23; p = 0.180). The similarity of MACEs between the two groups was consistent across a variety of subgroups. Conclusions After adjusting for baseline differences, residual non-culprit LMCAD does not appear to increase the risk of MACEs at 12 months in patients undergoing emergent PCI for AMI complicated by CS.


Summary of clinical trial
1. 19 years old or older 2-1). Systolic blood pressure is less than 90mmHg for more than 30 minutes despite the fluid therapy, or Use of pressure boosting agents is necessary. . Peripheral hypopnea (cold skin, urine less than 30 cc per hour, impaired consciousness, lactate ≥2.0 mmol / l) or a person with pulmonary edema.

4.
In-hospital cardiac arrest as a result of the cause stated in 'inclusion criteria 3'.

5.
Those voluntarily consenting to the medical records and the data necessary for the study during the entire study period.

Detailed description
1) The selection / exclusion criteria for persons with cardiogenic shock should be verified by medical records from January 1, 2014 before the approval date of each institution's clinical trial screening committee.
2) If a cardiogenic shock to the selection criteria is found in the emergency room, general ward, or intensive care unit of the participating institutions, enroll in this study and fill in the information according to the e-CRF.
3) After 1, 6 and 12 months, visit the hospital for examination and procedures. The person in charge of the examination or the delegate of the examiner may follow the person by telephone or an outpatient visit.

Primary Endpoint
In-hospital death Clinical trial flow chart 1. There must be a signature from the patient or their legal guardian on the consent form. As this study is a retrospective and prospective registry study, data can be collected from patients who meet the selection criteria for either undergoing coronary angiography, insertion or non-insertion of a left ventricular assist device, after obtaining consent for access to medical records.
3. Investigate whether complications such as limb ischemia, stroke, sepsis, major bleeding events, vascular injury during insertion, and failure of left ventricular assist device insertion occurred. 4. CBC, Creatinine, Fasting glucose level, AST, ALT, T-bilirubin, LDH, Sodium 5. Lactate and ScVO2 are measured every 6 hours from the onset of shock, and then once a day until shock recovery.
* Telephone (landline) interviews are also allowed for information gathering without the subjects having to visit the hospital. Week ±4wks 48 Week ±4wks Obtaining consent X 1 Inclusion/exclusion criteria X accompanied by acute myocardial infarction for whom early coronary intervention was scheduled [2]. As a result, research on the effectiveness and safety of mechanical circulatory support devices that can more effectively assist left ventricular function in cardiogenic shock is being actively pursued worldwide [3][4][5][6]. In particular, the expected benefits of ECMO, a left ventricular assist device that can be operated anywhere in emergency situations, are significant, and interest in ECMO procedures is rapidly increasing in Korea, with the number of procedures increasing rapidly.
Therefore, it is urgent to evaluate the appropriateness and effectiveness of ECMO and conduct research on its effects. In addition, considering that the group with LVADs inserted is significantly superior to the group without LVADs, a one-sided test is usually performed, and when adjusted, the power exceeds 90%. Therefore, it is expected that this clinical trial plan will be statistically and clinically successful when executed.

Overview
Shock patients with cardiogenic shock caused by acute myocardial infarction, myocardial disease, myocarditis, etc. will be registered both retrospectively and prospectively for two and a half years before and after IRB approval. Patients undergoing coronary intervention and treatment are performed according to the standard method recommended by the Korean Society of Cardiology. If the patient satisfies the above conditions and meets other inclusion and exclusion criteria, we obtain the patient's consent and enroll them in the study. On the day of shock occurrence, we perform physical measurements, blood tests, investigate the medication being taken, and record the most severe signs of vitality on that day. The maximum dose of medication used for shock treatment, the insertion of a left ventricular assist device, and indicators of shock deterioration and improvement are followed up. We conduct tests scheduled for the day of shock occurrence and one month, six months, and twelve months afterward to confirm whether a death event occurred. If the subject is unable to visit the hospital due to unavoidable circumstances, the trial responsible person or the person delegated by the trial responsible person may follow-up and check the subject's survival status and death event by phone.

Insertion of left ventricular assist devices
The insertion of a left ventricular assist device is typically performed according to the recommendations of the

① Written informed consent for patients enrolled
According to the scope of data collection, it is divided into prospective data collection subjects and retrospective data collection subjects.
 Prospective data collection subjects: The day of shock occurrence is after the IRB approval date  Retrospective data collection subjects: The day of shock occurrence is before the IRB approval date For prospective data collection subjects, before entering the clinical trial, the purpose and content of the trial should be explained in detail to the subject or legal guardian (in the case of a subject who cannot provide consent for the trial), and the written consent form should accurately record the signature dates of the subject and investigator. The original signed consent form is kept by the subject, and a copy is provided to the subject. If the subject is unable to consent on the day of the shock occurrence, the consent form is obtained from the representative of the accompanying subject. In this case, the principal investigator and sub-investigator must inform the subject or the subject's representative about the clinical trial as soon as possible and obtain consent to continue participating in the trial. If the subject recovers to a condition where consent can be given, the consent form is obtained from the subject.
For retrospective data collection subjects, only data corresponding to the study protocol are collected until IRB approval is obtained without written consent. However, among shock occurrence subjects before IRB approval, those who have obtained written consent are eligible for both prospective and retrospective data collection.
② Inclusion/exclusion criteria Subjects should be reviewed by the investigator or their delegate to ensure that the subject is suitable for the study.

Primary Endpoint
In-hospital death

Statistical analysis
We aim to identify predictors of in-hospital death in patients who experience shock using binary logistic regression analysis. This type of analysis requires 10-15 events per independent variable, and with an expected mortality rate of about 40%, or approximately 400 deaths, we have sufficient events to study various risk factors. The goodness-of-fit of the model will be assessed using the C-statistic and Hosmer-Lemeshow test. In addition, we plan to compare the in-hospital death rate between patients with and without left ventricular assist devices using chi-square tests among those who receive a certain level of vasoactive drugs.
We also aim to identify predictors of successful removal of the ECMO device and procedure-related complications such as bleeding, thrombosis, and limb ischemia using binary logistic regression analysis in patients who undergo ECMO. Finally, we plan to evaluate overall death over five years using Cox survival Method of handling

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analysis. We will assess the goodness-of-fit of the model by checking Schoenfeld's residuals and identify the hazard of each risk factor.

Evaluation criteria for safety including side effects, and evaluation and reporting methods
Not applicable

Indemnity procedures for any harm
By participating in this clinical study, we do not provide any separate compensation for the treatment of predictable or unexpected side effects or complications that may occur. There is no financial compensation provided for participating in this clinical study, and the tests conducted are not tests performed specifically for the study, but rather tests that would be received during routine clinical care, whether or not the individual participates in the study. Therefore, any tests or consultation fees related to the clinical trial are the responsibility of the subject.

Criteria for the medical treatment of subjects after the clinical trial
After the 12-month study is completed, participants will continue to periodically visit the outpatient clinic according to each treatment provider's follow-up criteria to receive physical examinations and evaluations.
They will also receive ongoing education to seek immediate consultation in case of symptoms such as chest pain, heart failure, or arrhythmia. In the event of adverse reactions or the need for hospitalization, the researchers will make every effort to minimize the risk.

Protection of subject confidentiality
Records that can identify the subject will be kept confidential and will not be publicly disclosed. However, monitors, inspectors, review boards, and government agencies may directly access the subject's medical records or data within the scope permitted by relevant laws or regulations to verify the implementation procedures and reliability of the data of the clinical trial. Even in this case, confidentiality will be maintained as much as possible. The subject's signature on the consent form indicates permission for such direct access, and the subject's identity will be kept confidential when the results of the clinical trial are published.
Personal information such as the subject's name may be collected as a result of participation in this clinical trial, but this information will only be used for the purpose of linking to clinical information obtained SMART-RESCUE

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through the clinical trial and will not be directly used or required for the research. Therefore, the collected information will be used until the completion of the preparation of the clinical trial report and will be appropriately managed in accordance with the Personal Information Protection Act.

Method of data coding
In all documents related to clinical trials such as case records, the subject's name is recorded and

Informed consent form
Patients who have heard sufficient explanation about the study and have voluntarily written the informed consent form are eligible to participate in the clinical trial. If there are any changes regarding safety during the study, signatures must be obtained from all participants for the proposed modifications. Researchers must inform patients that they have the right to refuse participation freely and may withdraw from the study at any time without any future disadvantage to their treatment. If the patient is deemed to have understood the research participation sufficiently, the patient can sign the informed consent form. The researcher provides the patient with a copy of the signed informed consent form.